Correlations between cerebrospinal fluid biomarkers, neurocognitive tests, and resting-state electroencephalography (rsEEG) in patients with HIV-associated neurocognitive disorders.

HIV-associated neurocognitive disorders (HAND) are highly prevalent in people living with HIV (PLWH) despite successful treatment with combination antiretroviral therapy (cART). HAND pathogenesis is complex and definitive surrogate biomarkers are not clearly defined. Brain function has been assessed through the evaluation of cortical source rhythms with delta waves associated with neurological impairment. The aim of this study was to assess the correlation between EEG cortical sources, cerebrospinal fluid (CSF) biomarkers, and neurocognitive tests in PLWH with HAND. PLWH with HAND without significant comorbidities were enrolled. Baseline rsEEG-LORETA waves, CSF biomarkers (t-tau, p-tau, ß-amiloid42, neopterin, S100ß), and neurocognitive tests were correlated and compared through non-parametric tests (Spearman's rho and Mann-Whitney); data are presented as medians (interquartile ranges). Fifty-four patients were enrolled. Median time of suppressed HIV-RNA and CD4+ T-lymphocyte were 10 years (5.5-15) and 691/uL (477-929). Thirty-nine participants (72%) underwent CSF collection: abnormal biomarkers were found in a small percentage. Only neopterin showed a statistically significant correlation with delta activity [parietal (rho 0.579; p < 0.001), occipital (rho 0.493; p = 0.007), and global sources (rho 0.464 p = 0.011)]. Seven patients (12.9%) showed an abnormal neopterin level (> 1.5 ng/mL) with significantly higher delta source activity compared to the ones with in-range concentrations. We observed a statistically significant correlation between working memory test Trail Making B with both CSF neopterin levels and delta waves (p values < 0.05). In a small sample of PLWH with HAND, we observed that higher CSF neopterin levels were associated with higher EEG delta waves and worse working memory tests.

Heterogeneous Predisposing Factors and Etiology of Edema of the Uvula in a Spanish Population.

BACKGROUND AND OBJECTIVE: Edema of the uvula (EU) may appear in isolation or in association with clinical manifestations such as urticaria, angioedema, and anaphylaxis. EU may lead to upper airway obstruction, provoking obstructive respiratory distress and asphyxia. Objective: We sought to investigate the etiology of and predisposing factors for EU in a large population of patients referred to an outpatient clinic. METHODS: In this 3-year follow-up cohort study, 171 patients presenting with EU were identified and classified as having isolated EU or nonisolated EU. The etiology of each patient's condition was studied, and possible predisposing factors were recorded. An allergology work-up and a statistical study (bivariate/multivariate analyses) were performed. RESULTS: The predisposing factors for both groups of EU patients were found to be different. The etiology of the problem was identified for most patients; allergy to Anisakis simplex was the most common cause in both groups. Nonsteroidal anti-inflammatory drugs and antibiotics were also found to be triggers in both groups. CONCLUSIONS: Isolated EU was associated with snoring, an elongated uvula, and having experienced previous episodes of EU. We found no associations between groups of EU patients and gender, obesity, smoking, alcohol consumption, personal and family history of atopy, and obstructive sleep apnea. Allergy to A simplex was the most commonly recorded cause.

On the design and efficacy assessment of self-assembling peptide-based hydrogel-glycosaminoglycan mixtures for potential repair of early stage cartilage degeneration.

Peptide-based hydrogels are of interest for their potential use in regenerative medicine. Combining these hydrogels with materials that may enhance their physical and biological properties, such as glycosaminoglycans, has the potential to extend their range of biomedical applications, for example in the repair of early cartilage degeneration. The aim of this study was to combine three self-assembling peptides (P11 -4, P11 -8, and P11 -12) with chondroitin sulphate at two molar ratios of 1:16 and 1:64 in 130 and 230 mM Na+ salt concentrations. The study investigates the effects of mixing self-assembling peptide and glycosaminoglycan on the physical and mechanical properties at 37°C. Peptide alone, chondroitin sulphate alone, and peptide in combination with chondroitin sulphate were analysed using Fourier transform infrared spectroscopy to determine the ß-sheet percentage, transmission electron microscopy to determine the fibril morphology, and rheology to determine the elastic and viscous modulus of the materials. All of the variables (peptide, salt concentration, and chondroitin sulphate molar ratio) had an effect on the mechanical properties, ß-sheet formation, and fibril morphology of the hydrogels. P11 -4 and P11 -8-chondroitin sulphate mixtures, at both molar ratios, were shown to have a high ß-sheet percentage, dense entangled fibrillar networks, as well as high mechanical stiffness in both (130 and 230 mM) Na+ salt solutions when compared with the P11 -12/chondroitin sulphate mixtures. These peptide/chondroitin sulphate hydrogels show promise for biomedical applications in glycosaminoglycan depleted tissues.

Anatomical variations of the celiac trunk: cadaveric and radiological study.

PURPOSE: The celiac trunk (CT) is a vascular structure of the upper abdomen which gives off the left gastric artery (LGA), the splenic artery and the common hepatic artery. This study aims to compare the vascular patterns of the CT of two different samples (cadaveric and radiological) and to propose a simple classification of CT variations based on previous studies and our results. MATERIALS AND METHODS: To perform this study we examined 43 adult cadavers, 24 males and 19 females, ages ranged from 69 to 92. In addition, we analysed 596 MDCT (multidetector computed tomographic) angiography examinations of 430 males and 166 females, ages ranged from 42 to 82. RESULTS: According to the classification proposed, results were divided into Type I or complete CT (578/639 cases, 90.5 %), Type II or incomplete CT (61/639 cases, 9.5 %), Type III or absence of CT and Type IV or celiacomesenteric trunk with no cases reported. Type I was divided into Type Ia or bifurcated trunk with LGA arising first (368/639 cases, 57.6 %), Type Ib or trifurcated trunk (205/639 cases, 32.1 %) and Type Ic or tetrafurcated trunk with an extra branch (5/639 cases, 0.8 %). Type II included hepatosplenic (29/639 cases, 4.5 %), gastroplenic (32/639, 5 %) and hepatogastric trunks (0/639, 0 %) which represented Types IIa, IIb and IIc respectively. CONCLUSIONS: No significant differences were found between the cadaveric and radiological samples. Gender did not appear to be related to any variability of the structures either. A new, simple and complete classification of the anatomical variations of the CT is proposed.

Histone acetylation deficits in lymphoblastoid cell lines from patients with Rubinstein-Taybi syndrome.

BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a congenital neurodevelopmental disorder defined by postnatal growth deficiency, characteristic skeletal abnormalities and mental retardation and caused by mutations in the genes encoding for the transcriptional co-activators with intrinsic lysine acetyltransferase (KAT) activity CBP and p300. Previous studies have shown that neuronal histone acetylation is reduced in mouse models of RSTS. METHODS: The authors identified different mutations at the CREBBP locus and generated lymphoblastoid cell lines derived from nine patients with RSTS carrying distinct CREBBP mutations that illustrate different grades of the clinical severity in the spectrum of the syndrome. They next assessed whether histone acetylation levels were altered in these cell lines. RESULTS: The comparison of CREBBP-mutated RSTS cell lines with cell lines derived from patients with an unrelated mental retardation syndrome or healthy controls revealed significant deficits in histone acetylation, affecting primarily histone H2B and histone H2A. The most severe defects were observed in the lines carrying the whole deletion of the CREBBP gene and the truncating mutation, both leading to a haploinsufficiency state. Interestingly, this deficit was rescued by treatment with an inhibitor of histone deacetylases (HDACi). CONCLUSIONS: The authors' results extend to humans the seminal observations in RSTS mouse models and point to histone acetylation defects, mainly involving H2B and H2A, as relevant molecular markers of the disease.

Four-month incidence of suicidal thoughts and behaviors among healthcare workers after the first wave of the Spain COVID-19 pandemic.

Healthcare workers (HCW) are at high risk for suicide, yet little is known about the onset of suicidal thoughts and behaviors (STB) in this important segment of the population in conjunction with the COVID-19 pandemic. We conducted a multicenter, prospective cohort study of Spanish HCW active during the COVID-9 pandemic. A total of n = 4809 HCW participated at baseline (May-September 2020; i.e., just after the first wave of the pandemic) and at a four-month follow-up assessment (October-December 2020) using web-based surveys. Logistic regression assessed the individual- and population-level associations of separate proximal (pandemic) risk factors with four-month STB incidence (i.e., 30-day STB among HCW negative for 30-day STB at baseline), each time adjusting for distal (pre-pandemic) factors. STB incidence was estimated at 4.2% (SE = 0.5; n = 1 suicide attempt). Adjusted for distal factors, proximal risk factors most strongly associated with STB incidence were various sources of interpersonal stress (scaled 0-4; odds ratio [OR] range = 1.23-1.57) followed by personal health-related stress and stress related to the health of loved ones (scaled 0-4; OR range 1.30-1.32), and the perceived lack of healthcare center preparedness (scaled 0-4; OR = 1.34). Population-attributable risk proportions for these proximal risk factors were in the range 45.3-57.6%. Other significant risk factors were financial stressors (OR range 1.26-1.81), isolation/quarantine due to COVID-19 (OR = 1.53) and having changed to a specific COVID-19 related work location (OR = 1.72). Among other interventions, our findings call for healthcare systems to implement adequate conflict communication and resolution strategies and to improve family-work balance embedded in organizational justice strategies.

A molecular phylogenetic framework for the Muricidae, a diverse family of carnivorous gastropods.

With over 1600 extant described species, the Muricidae are one of the most species-rich and morphologically diverse families of molluscs. As predators of molluscs, polychaetes, anthozoans barnacles and other invertebrates, they form an important component of many benthic communities. Traditionally, the classification of muricids at specific and generic levels has been based primarily on shells, while subfamilies have been defined largely by radular morphology, although the composition and relationships of suprageneric groups have never been studied exhaustively. Here we present the phylogenetic relationships of 77 muricid species belonging to nine of the ten currently recognized subfamilies, based on Bayesian inference and Maximum Likelihood analyses of partial sequences of three mitochondrial (12S, 16S and COI) and one nuclear (28S) genes. The resulting topologies are discussed with respect to traditional subfamilial arrangements, and previous anatomical and molecular findings. We confirm monophyly of each of the subfamilies Ergalataxinae, Rapaninae, Coralliophilinae, Haustrinae, Ocenebrinae and Typhinae as previously defined, but earlier concepts of Muricinae, Trophoninae and Muricopsinae are shown to be polyphyletic. Based on our phylogenetic hypothesis, a new arrangement of these subfamilies is proposed.

[Epidemiology and public health in the COVID-19 epidemic]. / Epidemiología y salud pública en la epidemia de la COVID-19.

In the last year, all have suffered the devastating consequences of the SARS-CoV-2 epidemic. Over the course of a few months, the news media has bombarded us with messages about incidences, lethality, or even more technical measurements such as R0 or the attack rate. With this update, we hope to clarify basic concepts on the dynamic of the epidemic as well as present what is known about it as of the time of writing. To do so, the information available from international bodies such as the World Health Organization as well as the Ministry of Health has been extracted and used. In no case is it to be understood as a fixed or known situation; it is a situation that, in contrast, is invariably changeable.

The Rubinstein-Taybi syndrome: modeling mental impairment in the mouse.

Mental impairment syndromes are diagnosed based on below-average general intellectual function originated during developmental periods. Intellectual abilities rely on the capability of our brain to obtain, process, store and retrieve information. Advances in the past decade on the molecular basis of memory have led to a better understanding of how a normal brain works but also have shed new light on our understanding of many pathologies of the nervous system, including diverse syndromes involving mental impairment. The recent multidisciplinary analysis of various mouse models for Rubinstein-Taybi syndrome has shown the power of animal models to produce an important leap forward in our understanding of a complex mental disease while simultaneously opening new avenues for its treatment. These studies also suggest that some of the cognitive and physiological deficits observed in mental impairment syndromes may not simply be caused by defects originated during development but may result from the continued requirement of specific enzymatic activities throughout life.

Cloning and inducible synthesis of poliovirus non-structural proteins in Saccharomyces cerevisiae.

Several coding regions of the poliovirus (PV) genome were cloned in the yeast Saccharomyces cerevisiae, and placed under the control of the inducible hybrid promoter pGAL/CYC, such that expression was triggered by incubating the cells in galactose (Gal)-containing medium. A number of PV genes encoding non-structural proteins, including 2Apro, 2B, 2C, 3A, 3AB and 3Cpro, were cloned and expressed in this eukaryotic system. The presence of these proteins after induction was detected by immunoblot analysis using specific antisera against each protein. The levels and the kinetics of protein synthesis after induction varied according to the PV protein analyzed. Thus, 2C was detected soon after Gal addition (3-5 h) and was one of the major polypeptides synthesized by yeast cells after 16 h of induction. In contrast, only low levels of synthesis were observed for 3A or 3AB, and then only after several hours of growth in Gal. The induction of the PV protease, 2Apro, was highly toxic for the cells such that growth was arrested after 5 h of induction and cell survival sharply declined.

Poliovirus 2Apro expression inhibits growth of yeast cells.

Poliovirus encodes two proteases, 2Apro and 3Cpro that participate in the processing of the viral polyprotein and cleave a number of host proteins. Both proteases have been cloned and expressed in an inducible manner in Saccharomyces cerevisiae cells. The expression of 2Apro, but not 3Cpro, was highly toxic for yeast cells such that growth was arrested after 5 h of induction and cell survival sharply declined. Cellular morphology was profoundly modified by expression of poliovirus 2Apro, in such a way that electron dense granules and autophagosomic bodies arise in the cytoplasm. Experiments aimed at defining the yeast function affected by 2Apro suggested that translation was not the target of protease toxicity, but showed that RNA synthesis was profoundly blocked.

Azaprostaglandin analogues. Synthesis and biological properties of 11-azaprostaglandin derivatives.

New nitrogen analogues of prostaglandins (11, 11a, 12, and 12a) have been synthesized starting from a 4,5-disubstituted 2-pyrrolidinone nucleus (5 and 5a) containing one side chain and a suitable functionality for elaborating the second one. These analogues had no better activity than natural prostaglandins in vitro [guinea pig ileum and trachea, rat stomach fundus strip, uterus and portal vein, ADP-induced guinea pig platelet-rich plasma (PRP) aggregation]. They similarly lacked any interesting activity in vivo [anesthetized rat blood pressure, stress, and acetylsalycilic acid (ASA) induced gastric lesions in rat].

Synthesis and prostaglandin-like activity of 2-(trans-3-hydroxy-1-octenyl)-3-indoleheptanoic acid.

The synthesis of 2-(trans-3-hydroxy-1-octenyl)-3-indoleheptanoic acid (1) is described. The title compound appeared to show a weak prostaglandin-like activity in two different systems. It contracted rat stomach fundus strips and guinea-pig ileum preparations only at concentrations about 10(3)- and 10(2)-fold higher, respectively, than PGE1. Moreover, it stimulated adenylate cyclase from rat liver plasma membrane, but the relative potency was 4--5 X 10(2)-fold lower than the natural compound. The title compound showed also a certain degree of PGE1 antagonism.

[Friedreich's ataxia: analysis of magnetic resonance imaging parameters and their correlates with cognitive and motor slowing]. / Ataxia de Friedreich: análisis de parámetros de resonancia magnética y correlatos con el enlentecimiento cognitivo y motor.

INTRODUCTION: The heredodegenerative ataxias are a heterogeneous group of disorders affecting especially the cerebellum and its tracts. Magnetic resonance imaging (MRI) studies using quantitative methodology are scarce, particularly in Friedreich's ataxia (FA). On the other hand, slowness of information processing speed has been described in FA, but no empirical relation with MRI parameters has been established. OBJECTIVE: The aim of the present study was to quantitatively assess infra and supratentorial atrophy in patients with clinical diagnosis of FA and to establish the relationship with a information processing speed measure. PATIENTS AND METHODS: Twelve FA patients that fulfilled clinical diagnostic criteria and twelve control subjects were studied. A computerized system that differentiate reaction time and movement time, as well as a semiautomated technique of binarization and analysis of MRI were used. RESULTS: Patients showed a poorer performance in movement time and in reaction time. Analyzing the frequency of pathologic changes, vermal atrophy was present in 67% of the patients and cerebellar hemisphere atrophy in 50%. Only a minority of patients showed signs of supratentorial cerebral atrophy (17%). Statistically significant negative correlations were obtained between reaction time and the size of the cerebellum. CONCLUSIONS: Cerebellar hemisphere atrophy is a usual finding in FA, although vermal atrophy is more frequent. The relation between cerebellar atrophy and reaction time supports the claim about cerebellar involvement in the information processing and response speed.

[Multiple sclerosis and depression]. / Esclerosis multiple y depresion.

INTRODUCTION: Depression has frequently been reported in multiple sclerosis. However, prevalence rates must be interpreted in the light of the conceptual and methodological limitations of these studies. Depression has traditionally been associated with response to the diagnosis of this disease, the presence of physical and cognitive limitations, the damage of specific neural systems and inmunomodulatory therapy. AIMS: To assess the evolution of emotional state and its relationship with motor and cognitive slowness, in relapsing remitting patients with minimal levels of neurological disability. PATIENTS AND METHODS: Data are reported for 35 patients with relapsing remitting multiple sclerosis, 27 treated with interferons and 8 without interferon treatment. Mood disturbance (Beck Depression Inventory, BDI), physical disability (Kurtzke Expanded Disability Status Scale, EDSS) and speed of information processing (reaction times) were assessed. The first testing was carried out before the start of treatment and the second testing one year later. RESULTS AND CONCLUSIONS: The group of patients showed a total BDI score indicative of minimal depression associated with items expressing performance difficulties and somatic complaints. Emotional state was not related to physical disability but was related to processing speed measures. A significant improvement of depression was observed after one year of treatment with inmunomodulatory therapy.

[Transient ischemic attacks: risk factors, duration and neuroimaging in a series of 173 patients]. / Ataques isquémicos transitorios: factores de riesgo, duración y neuroimagen en una serie de 173 pacientes.

INTRODUCTION: The appearance of transient ischemic attacks (TIA) is an important sign of vascular risk. The maximum time the deficit lasts has been set arbitrarily at 24 hours. It is assumed that TIA does not entail permanent vascular lesions. PATIENTS AND METHODS: A retrospective review of the clinical records of patients diagnosed as suffering from TIA in our centre between 1996 and 1997. Analysis of associated risk factors (RF), duration and findings in neuroimaging. RESULTS: The clinical records of 173 patients (106 males) were examined. The RF identified were similar to those described for ischemic strokes. 45.6% of patients with a history of vascular pathologies received no preventative treatment. 58% of the TIA were resolved within the first 30 minutes and 71% within the first hour. Cranial CT was normal in 69%, showed old lesions in 26% and lesions that were compatible with the clinical signs of TIA in 5% (in the latter case the duration of the episodes was greater). CONCLUSIONS: TIA shares the same RF and aetiopathogenic mechanisms as ischemic stroke and should, therefore, be considered as such. There is a need to revise the concept of TIA paying special attention to the findings of neuroimaging or to establish duration limits that are better matched to the practical reality. TIA maintains a practical interest since it provides a simple method of identifying patients with a high vascular risk.

[Event related brain potentials and imageability effect in the semantic processing]. / Potenciales evocados cerebrales asociados al efecto de imaginabilidad en el procesamiento semántico.

INTRODUCTION: Event-related brain potentials (ERPs) are a useful measure of the brain activity underlying linguistic processing. They can also be used to study cognitive/linguistic impairment in different neurological diseases. To do this, it is necessary to know which electrophysiological components are related to relevant linguistic parameters, and the characteristics of these components. One of these parameters is the dimension of concrete-abstract or imageability. AIM: To find electrophysiological evidence for differential processing of concrete vs abstract verbal material, in the absence of brain damage. SUBJECTS AND METHODS: The short, semantically congruent sentences used were made up of high or low imageability (HI/LI) verbs followed by HI/LI complements. We also manipulated close probability in the case of the complement. Sentences were shown word by word and participants were asked to make an imageability judgement. Electrophysiological recording during verb and final complement were analysed in ten subjects. RESULTS: Electrophysiological recording obtained during verb presentation show an imageability effect starting at 350 ms (especially in the N400 component) with no differential scalp distribution. There is a similar tendency in the recordings of final complements, although differences in imageability are not statistically significant. CONCLUSIONS: These results suggest the existence of an imageability effect in the ERPs associated with semantic processing in semantically congruent sentences and that this effect is produced when the verb is presented.

Variability in electromagnetic field levels over time, and Monte-Carlo simulation of exposure parameters.

This article analyses the electric field levels around medium-wave transmitters, delimiting the temporal variability of the levels received at a pre-established reception point. One extensively used dosimetric criterion is to consider historical levels of the field recorded over a certain period of time so as to provide an overall perspective of radio-frequency electric field exposure in a particular environment. This aspect is the focus of the present study, in which the measurements will be synthesised in the form of exposure coefficients. Two measurement campaigns were conducted: one short term (10 days) and the other long term (1 y). The short-term data were used to study which probability density functions best approximate the measured levels. The long-term data were used to compute the principal statistics that characterise the field values over a year. The data that form the focus of the study are the peak traces, since these are the most representative from the standpoint of exposure. The deviations found were around 6 % for short periods and 12 % for long periods. The information from the two campaigns was used to develop and implement a computer application based on the Monte Carlo method to simulate values of the field, allowing one to carry out robust statistics.

[Normalisation and validation of the Brief Neuropsychological Battery as the reference neuropsychological test in multiple sclerosis]. / Normalizacion y validacion de la bateria neuropsicologica breve como test neuropsicologico de referencia en la esclerosis multiple.

INTRODUCTION. The current batteries such as the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) for evaluating cognitive decline in patients with multiple sclerosis are complex and time-consuming. AIM. To obtain normative values and validate a new battery. SUBJECTS AND METHODS. Four neuropsychological tests were finally included (episodic memory, the Symbol-Digit Modalities Test, a category fluency test, and the Paced Auditory Serial Addition Test). Normative values (overall and by age group) were derived by administering the battery to healthy subjects (5th percentile was the limit of normal). External validity was explored by comparison with the BRB-N. The new battery was also administered to a subsample after 4 weeks to assess reproducibility. RESULTS. To provide normative data, 1036 healthy subjects were recruited. The mean completion time was 18.5 ± 5.2 minutes. For the 229 subjects who were administered the new battery and the BRB-N, no statistically significant differences were found except for mean completion time (19 ± 4 vs 25 ± 5 minutes). In the reproducibility study, there were no significant differences except in the memory tests. CONCLUSION. The scores on the new battery and the BRB-N were strongly correlated although the shorter completion time and ease of administration could make the new battery preferable in clinical practice.

Primary care randomized clinical trial: manual therapy effectiveness in comparison with TENS in patients with neck pain.

This study investigated effectiveness of manual therapy (MT) with transcutaneous electrical nerve stimulation (TENS) to reduce pain intensity in patients with mechanical neck disorder (MND). A randomized multi-centered controlled clinical trial was performed in 12 Primary Care Physiotherapy Units in Madrid Region. Ninety patients were included with diagnoses of subacute or chronic MND without neurological damage, 47 patients received MT and 43 TENS. The primary outcome was pain intensity measured in millimeters using the Visual Analogue Scale (VAS). Also disability, quality of life, adverse effects and sociodemographic and prognosis variables were measured. Three evaluations were performed (before, when the procedure finished and six months after). Seventy-one patients (79%) completed the follow-up measurement at six months. In more than half of the treated patients the procedure had a clinically relevant "short term" result after having ended the intervention, when either MT or TENS was used. The success rate decreased to one-third of the patients 6 months after the intervention. No differences can be found in the reduction of pain, in the decrease of disability nor in the quality of life between both therapies. Both analyzed physiotherapy techniques produce a short-term pain reduction that is clinically relevant.